Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy.
Mike Wenzel, Florestan Koll, Benedikt Hoeh, Clara Humke, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Amir Sabet, Daniel Gröner, Felix K H Chun, Philipp Mandel
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Abstract
Purpose: Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.
Materials and methods: We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen (BRCA) or tumor suppressor gene mutations (TP53, PTEN, RB1). Specifically, subgroup analyses were performed for patients with Lu-PSMA-treated mCRPC.
Results: Of 194 patients with mCRPC, 22% was BRCA1/2 versus 14% PTEN/TP53/RB1 versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to BRCA and PTEN/TP53/RB1 patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for BRCA versus PTEN/TP53/RB1 versus no mutated patients (P < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; P < .01), whereas PTEN/TP53/RB1 patients were not (P = .4). Of 87 patients with Lu-PSMA-treated mCRPC, significant differences in PFS and OS were observed (both P ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas PTEN/TP53/RB1 patients had similar outcomes as no mutated patients.
Conclusion: In real-world setting, substantially lower OS in mCRPC is observed for BRCA- and PTEN/TP53/RB1-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for BRCA patients.
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